Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

Enzymatic transition state poise and transition state analogues

The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (A(N)D(N) or S(N)2), aromatic nucleophilic displacements (A(N)D(N) or S(N)Ar), and both concerted and stepwise dissociative nucleophilic displacements (D(N)A(N) and D(N)A(N); S(N)1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (S(N)2 or D(N)A(N)) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric nucleophilic displacements at carbon have been described. Enzymatic transition state poise is summarized in a single diagram of bond orders using the terminology of Jencks. The analysis reveals enzymatic contributions to transition state poise, provides precedent for assignment of reaction types, and summarizes the current status of the experimental characterization of enzymatic transition states. Binding strengths of transition state analogues are readily correlated with transition state poise.     

胶管胶带用硫化剂和防老剂

越来越高的汽车发动机温度对在汽车中使用的胶管和胶带用聚合物提出了更严格的要求。本综述了胶管和胶带中使用的聚合物，并针对提高耐热、耐屈挠疲劳和耐臭氧老化性能讨论了每一种聚合物用的硫化体系和防老剂搭配。     

Vegetation water content during SMEX04 from ground data and Landsat 5 Thematic Mapper imagery

Vegetation water content is an important parameter for retrieval of soil moisture from microwave data and for other remote sensing applications. Because liquid water absorbs in the shortwave infrared, the normalized difference infrared index (NDII), calculated from Landsat 5 Thematic Mapper band 4 (0.76-0.90 μm wavelength) and band 5 (1.55-1.65 μm wavelength), can be used to determine canopy equivalent water thickness (EWT), which is defined as the water volume per leaf area times the leaf area index (LAI). Alternatively, average canopy EWT can be determined using a landcover classification, because different vegetation types have different average LAI at the peak of the growing season. The primary contribution of this study for the Soil Moisture Experiment 2004 was to sample vegetation for the Arizona and Sonora study areas. Vegetation was sampled to achieve a range of canopy EWT; LAI was measured using a plant canopy analyzer and digital hemispherical (fisheye) photographs. NDII was linearly related to measured canopy EWT with an R² of 0.601. Landcover of the Arizona, USA, and Sonora, Mexico, study areas were classified with an overall accuracy of 70% using a rule-based decision tree using three dates of Landsat 5 Thematic Mapper imagery and digital elevation data. There was a large range of NDII per landcover class at the peak of the growing season, indicating that canopy EWT should be estimated directly using NDII or other shortwave-infrared vegetation indices. However, landcover classifications will still be necessary to obtain total vegetation water content from canopy EWT and other data, because considerable liquid water is contained in the non-foliar components of vegetation.     

Synthesis and characterization of coprecipitation-derived ferrimagnetic glass-ceramic

Ferrimagnetic glass-ceramics could be used for magnetic induction hyperthermia. This technique is utilised for the destruction of solid neoplastic diseases by application of an alternating magnetic field. Biocompatible ferrimagnetic materials could be easily incorporated into a tumour and could generate heat mainly by hysteresis loss. A ferrimagnetic glass-ceramic in the system SiO₂–Na₂O–CaO–P₂O₅–FeO–Fe₂O₃ has been prepared by melting of the coprecipitation-derived raw materials. This glass-ceramic contains a unique crystalline phase, magnetite, embedded in an amorphous matrix. Magnetite crystals precipitate during cooling from melting temperature. This glass-ceramic would no longer require any nucleation and growth thermal treatment, since the maximal quantity of magnetite crystals was produced during cooling. The average unit-cell parameter, crystallite size of magnetite, and the quantitative ratio of the crystallographic phases in the glass-ceramic samples were evaluated using two different methods. Similar results were obtained with both methods. The magnetite crystals are about 50 nm in dimensions. The samples contain 45 wt% of magnetite, homogeneously distributed in the amorphous residual matrix. The as prepared glass-ceramic has a saturation magnetisation of 34 A·m²/kg and a coercive force of 6.7 kA/m. The estimated magnetic loss/cycle under the magnetic field up to 796 kA/m is around 1.45 mJ/g. The specific power loss of this glass-ceramic under a magnetic field of 40 kA/m and a frequency of 440 kHz is 25 W/g. This material showed a bioactive behaviour, as after 2 weeks of soaking in a simulated body fluid the formation of a hydroxylapatite layer on their surface was observed. This feature makes it also suitable for bone cancer.     

Digital light processing stereolithography of hydroxyapatite scaffolds with bone-like architecture,permeability, and mechanical properties

This work deals with the additive manufacturing and characterization of hydroxyapatite scaffolds mimicking the trabecular architecture of cancellous bone. A novel approach was proposed relying on stereolithographic technology, which builds foam-like ceramic scaffolds by using three-dimensional (3D) micro-tomographic reconstructions of polymeric sponges as virtual templates for the manufacturing process. The layer-by-layer fabrication process involves the selective polymerization of a photocurable resin in which hydroxyapatite particles are homogeneously dispersed. Irradiation is performed by a dynamic mask that projects blue light onto the slurry. After sintering, highly-porous hydroxyapatite scaffolds (total porosity ~0.80, pore size 100-800 µm) replicating the 3D open-cell architecture of the polymeric template as well as spongy bone were obtained. Intrinsic permeability of scaffolds was determined by measuring laminar airflow alternating pressure wave drops and was found to be within 0.75-1.74 × 10⁻⁹ m², which is comparable to the range of human cancellous bone. Compressive tests were also carried out in order to determine the strength (~1.60 MPa), elastic modulus (~513 MPa) and Weibull modulus (m = 2.2) of the scaffolds. Overall, the fabrication strategy used to print hydroxyapatite scaffolds (tomographic imaging combined with digital mirror device [DMD]-based stereolithography) shows great promise for the development of porous bioceramics with bone-like architecture and mass transport properties.     

Foam-like scaffolds for bone tissue engineering based on a novel couple of silicate-phosphate specular glasses: synthesis and properties

Glass–ceramic scaffolds mimicking the structure of cancellous bone were produced via sponge replication technique by using a polyurethane foam as template and glass powder below 30 μm as inorganic phase. Specifically, a SiO₂-based glass of complex composition and its corresponding P₂O₅-based “specular” glass were used as materials for scaffolding. The polymeric sponge was thermally removed and the glass powders were sintered to obtain a replica of the template structure. The scaffolds were investigated and compared from a structural, morphological and mechanical viewpoint by assessing their crystalline phases, volumetric shrinkage, pores content and interconnection, mechanical strength. In addition, the scaffolds were soaked in acellular simulated body fluid to investigate their in vitro behaviour. The produced scaffolds have a great potential for bone reconstructive surgery because their features, such as shape, strength, bioactivity and bioresorption, can be easily tailored according to the end use.     

Na2O-CaO-SiO2 glass-ceramic matrix biocomposites

Na₂O-CaO-SiO₂ glass- and glass-ceramic matrix/Ti particle biocomposites have been prepared by means of two processes: pressureless sintering and hot pressing. Time and temperature sintering conditions were optimised on the basis of the thermal properties of mixed glass and Ti powders, determined by Differential Thermal Analysis, Differential Scanning Calorimetry, Hot Stage Microscopy, Dilatometry. Each sintered sample was characterised by means of X-ray diffraction, Scanning Electron Microscopy, EDS, density measurements, Young's modulus, induced crack propagation by Vickers indentations, three point bending test, K _IC measurements. The in vitro bioactivity was investigated on the sintered composites by soaking them in a simulated body fluid (SBF) with the same ion concentration of the human plasma.